Last week, Cancer Research UK-funded scientists discovered a simple test that can reveal whether relatives of bowel cancer patients are themselves at high risk of the disease.

Identifying these people, and offering them screening from a relatively young age, could save lives.

Let’s look at the story in more detail.

Family history
Our genes have a big impact on bowel cancer risk, acting in combination with lifestyle factors such as diet, bodyweight and physical activity. And we know that people with a family history of bowel cancer are at greater risk than the general population.

In fact, studies show that you’re twice as likely to develop bowel cancer if you have a first-degree relative (parent, child or sibling) with the disease – more so if they were diagnosed under the age of 45.

People from a small number of families with a very strong history of bowel cancer due to faults in certain genes are already offered regular colonoscopy screening from the age of 25. And in 2005, our researchers showed that offering a colonoscopy to people with even a moderate family history of bowel cancer from the age of 45 could save lives.

So why not offer a colonoscopy to everyone with a family history of the disease? Or everyone with even one close relative with bowel cancer?

Impractical, uncomfortable and expensive
For a start, having a family history of bowel cancer isn’t a guarantee that you are at risk. Due to the way that genetic inheritance works, there is a 50:50 chance that you won’t have inherited a gene fault responsible for increased risk. This means that many people would go through the screening process unnecessarily, and having a colonoscopy isn’t exactly pleasant.

In addition, it’s simply not practical. Colonoscopy requires specialist equipment and trained staff, and there are many thousands of people who would potentially be eligible for screening. 36,500 people are diagnosed with bowel cancer every year in the UK, meaning many times more relatives to be tested.

At the moment, the NHS simply couldn’t cope with the demand. And even offering stool testing (the faecal occult blood test, FOBT) for thousands of extra people would still put a lot of pressure on the national screening service. Currently, bowel screening by FOBT is offered to people in their sixties across most of the UK.

So we need to find the people who are at genetically high risk of bowel cancer – and this is where the new research comes into play.

Genes, risk and screening
In a study published in the Journal of Clinical Oncology, PhD student Steven Lubbe and his colleagues at the Institute of Cancer Research investigated nearly 3,000 people with bowel cancer, together with 17,000 of their first-degree relatives (parents, siblings and children).

These people were already part of much larger UK National Study of Colorectal Cancer Genetics, a study that has been running since 2003 and hopes to answer some of the mysteries of why some people get bowel cancer and others don’t.

In the new study, the researchers tested DNA taken from tumour samples from the patients, looking for signs of type of DNA damage called ‘microsatellite instability’, caused by faults in genes that repair DNA damage.

The scientists found that nearly 350 of the original 3,000 patients had significant levels of this DNA damage, and that these people tended to develop bowel cancer at a younger age.

Importantly, they also found that the immediate relatives of these people were at higher risk of developing bowel cancer than the relatives of patients whose cancer didn’t have damaged DNA.

This was especially true if the patient was diagnosed with bowel cancer at a young age. For example, if a person was diagnosed with bowel cancer under the age of 45, and they didn’t have signs of this specific tell-tale DNA damage, the risk of a 40-year-old relative developing the disease was less than one in a hundred. But if their tumour’s DNA was faulty, then the risk was around nine times higher.

According to this study, bowel cancer seems to be twenty times more common in first degree relatives of younger patients with this specific form of DNA damage, than it is in the general population.

What does this mean for families affected by bowel cancer?
By identifying relatives at greatest risk, these new results help to show us where we could focus screening efforts. Between one and five per cent of families with a history of bowel cancer are likely to fall into this high risk category.

This may seem small, percentage-wise – but because bowel cancer is so common, this is actually quite a lot of people. So targeting screening to these people could save a significant number of lives.

Based on their results, the researchers suggest colonoscopy should be offered to first-degree relatives of patients whose tumours show signs of microsatellite instability, especially if they were diagnosed relatively young. They also think that screening in this way should start from the age of 25.

On the flip-side, the research also tells us that relatives of people whose bowel cancers don’t have this damage are unlikely to need screening from such a young age.

When we are born, we’re dealt a hand of genetic ‘cards’. Some people get a great hand, others get a bad one.

The trick is to find ways of singling out the people with a ‘bad hand’, and helping them play their cards well, by offering them targeted cancer screening and prevention measures. That will reduce the impact cancer will have on their lives, and prevent more early deaths from bowel cancer.

Kat

References:

Butterworth, A. et al (2006). Relative and absolute risk of colorectal cancer for individuals with a family history: A meta-analysis European Journal of Cancer, 42 (2), 216-227 DOI: 10.1016/j.ejca.2005.09.023

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